TY - JOUR
T1 - A Preliminary Randomized Double Blind Placebo-Controlled Trial of Intravenous Immunoglobulin for Japanese Encephalitis in Nepal
AU - Rayamajhi, Ajit
AU - Nightingale, Sam
AU - Bhatta, Nisha Keshary
AU - Singh, Rupa
AU - Ledger, Elizabeth
AU - Bista, Krishna Prasad
AU - Lewthwaite, Penny
AU - Mahaseth, Chandeshwar
AU - Turtle, Lance
AU - Robinson, Jaimie Sue
AU - Galbraith, Sareen Elizabeth
AU - Wnek, Malgorzata
AU - Johnson, Barbara Wilmot
AU - Faragher, Brian
AU - Griffiths, Michael John
AU - Solomon, Tom
PY - 2015/4/17
Y1 - 2015/4/17
N2 - BackgroundJapanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG’s anti-inflammatory properties may also be beneficial.Methodology/Principal FindingsWe performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group.Conclusions/SignificanceA trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study.
AB - BackgroundJapanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG’s anti-inflammatory properties may also be beneficial.Methodology/Principal FindingsWe performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group.Conclusions/SignificanceA trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study.
U2 - 10.1371/journal.pone.0122608
DO - 10.1371/journal.pone.0122608
M3 - Article
VL - 10
SP - e0122608
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e0122608
ER -